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Journal of Virology, March 2009, p. 2246-2254, Vol. 83, No. 5
0022-538X/09/$08.00+0 doi:10.1128/JVI.02234-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Level of Herpes Simplex Virus Type 1 Latency Correlates with Severity of Corneal Scarring and Exhaustion of CD8+ T Cells in Trigeminal Ganglia of Latently Infected Mice
Kevin R. Mott,1
Catherine J. Bresee,1
Sariah J. Allen,1
Lbachir BenMohamed,2,3,4
Steven L. Wechsler,2,5,6 and
Homayon Ghiasi1*
Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, CSMC Burns & Allen Research Institute, Los Angeles, California,1 Virology Research, The Gavin S. Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, California 92697,2 Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, California 92697,3 Center for Immunology, University of California Irvine, Irvine, California 92697,4 Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, California 92697,5 Center for Virus Research, University of California Irvine, Irvine, California 926976
Received 22 October 2008/ Accepted 9 December 2008
A hallmark of infection with herpes simplex virus type 1 (HSV-1) is the establishment of latency in ganglia of the infected individual. During the life of the latently infected individual, the virus can occasionally reactivate, travel back to the eye, and cause recurrent disease. Indeed, a major cause of corneal scarring (CS) is the scarring induced by HSV-1 following reactivation from latency. In this study, we evaluated the relationship between the amount of CS and the level of the HSV-1 latency-associated transcript (LAT) in trigeminal ganglia (TG) of latently infected mice. Our results suggested that the amount of CS was not related to the amount of virus replication following primary ocular HSV-1 infection, since replication in the eyes was similar in mice that did not develop CS, mice that developed CS in just one eye, and mice that developed CS in both eyes. In contrast, mice with no CS had significantly less LAT, and thus presumably less latency, in their TG than mice that had CS in both eyes. Higher CS also correlated with higher levels of mRNAs for PD-1, CD4, CD8, F4/80, interleukin-4, gamma interferon, granzyme A, and granzyme B in both cornea and TG. These results suggest that (i) the immunopathology induced by HSV-1 infection does not correlate with primary virus replication in the eye; (ii) increased CS appears to correlate with increased latency in the TG, although the possible cause-and-effect relationship is not known; and (iii) increased latency in mouse TG correlates with higher levels of PD-1 mRNA, suggesting exhaustion of CD8+ T cells.
* Corresponding author. Mailing address: Center for Neurobiology and Vaccine Development—CSMC Burns & Allen Research Institute, D2024, 8700 Beverly Blvd., Los Angeles, CA 90048. Phone: (310) 423-0593. Fax: (310) 423-0302. E-mail: ghiasih{at}CSHS.org
Published ahead of print on 17 December 2008.
Journal of Virology, March 2009, p. 2246-2254, Vol. 83, No. 5
0022-538X/09/$08.00+0 doi:10.1128/JVI.02234-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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